Glucocorticoid- β-adrenoceptors interactions in the infralimbic cortex in acquisition and consolidation of auditory fear memory extinction in rats

This study investigated the interactive effect of glucocorticoid and β-adrenoceptors in the infralimbic (IL) cortex on the acquisition and consolidation of fear extinction in rats' auditory fear conditioning (AFC) task. On day 1, rats underwent habituation for 9 min (12 tones, 10 s, 4 kHz, 80 dB, without footshock). On day 2 (conditioning), rats received 3 mild electrical footshocks (US; 2 s, 0.5 mA) paired with the auditory-conditioned stimulus (CS; tone: 30 s, 4 kHz, 80 dB). On days 3–5 (Ext 1–3), rats received 15 tones with no footshock in the test box. Intra-IL injection of corticosterone (CORT, 20 ng/0.5 μl per side) before Ext 1 and after Ext 1–2, respectively, facilitated the acquisition and consolidation of fear memory extinction. Intra-IL injection of the β₂-adrenoceptor agonist clenbuterol (CLEN, 50 ng/0.5 μl per side) inhibited, but the β-adrenoceptor antagonist propranolol (PROP, 500 ng/0.5 μl per side) enhanced the facilitatory effects of CORT on fear memory extinction. CORT injection before the acquisition of fear extinction increased p-ERK levels in the IL. Co-injection of CORT with CLEN increased, but PROP decreased p-ERK activities. CORT injection after the consolidation of fear extinction increased p-CREB in the IL. Co-injection of CORT with CLEN increased, but PROP reduced p-CREB activities. Our findings show that corticosterone facilitates the acquisition and consolidation of fear memory extinction. GRs and β-adrenoceptors in the IL jointly regulate fear memory extinction via ERK and CREB signaling pathways. This pre-clinical animal study may highlight the effect of GRs and β-adrenoceptors of the IL cortex in regulating fear memory processes in fear-related disorders such as PTSD.